eCAM Advance Access published online on March 17, 2009
eCAM, doi:10.1093/ecam/nep020
Inhibition of Anchorage-Independent Proliferation and G0/G1 Cell-Cycle Regulation in Human Colorectal Carcinoma Cells by 4,7-Dimethoxy-5-methyl-l,3-benzodioxole Isolated from the Fruiting Body of Antrodia camphorate
1Department of Chemistry, Tunghai University, Taichung, 2Graduate Institute of Biomedical Technology, Taipei Medical University, Taipei, 3Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan, 4Graduate Institute of Neuroscience, Taipei Medical University, Taipei and 5Department of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
In this study, 4,7-dimethoxy-5-methyl-l,3-benzodioxole (SY-1) was isolated from three different sources of dried fruiting bodies of Antrodia camphorate (AC). AC is a medicinal mushroom that grows on the inner heartwood wall of Cinnamomum kanehirai Hay (Lauraceae), an endemic species that is used in Chinese medicine for its anti-tumor and immunomodulatory properties. In this study, we demonstrated that SY-1 profoundly decreased the proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest (50–150 µM) and induction of apoptosis (>150 µM). Cell-cycle arrest induced by SY-1 was associated with a significant increase in levels of p53, p21/Cip1 and p27/Kip1, and a decrease in cyclins D1, D3 and A. In contrast, SY-1 treatment did not induce significant changes in G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC). The cells were cultured in soft agar to evaluate anchorage-independent colony formation, and we found that the number of transformed colonies was significantly reduced in the SY-1-treated COLO 205 cells. These findings demonstrate for the first time that SY-1 inhibits human colon cancer cell proliferation through inhibition of cell growth and anchorage-independent colony formation in soft agar. However, the detailed mechanisms of these processes remain unclear and will require further investigation.
Keywords: Antrodia camphorate – apoptosis – colon cancer – G0/G1 cell-cycle arrest – soft agar assay
For reprints and all correspondence: Yuan-Soon Ho, Graduate Institute of Biomedical Technology, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 110, Taiwan. Tel: +886-2-27361661. Ext. 3327; Fax: +886-2-2739-3422; E-mail: hoyuansn{at}tmu.edu.tw or Ya-Yun Lai, Department of Applied Chemistry, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Rd., Taichung 402, Taiwan. Tel: +886-4-24730022. Ext. 11873; Fax: +886-4-23248189; E-mail: yayun819{at}csmu.edu.tw